This is the second renewal of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center (Bryan ADRC), at Duke University Medical Center, Durham, NC: Allen D. Roses. M.D., Principal Investigator and Director, Donald E. Schmechel, M.D. and Kathleen A. Welsh. Ph.D.. Associate Directors. The overall specific aims of the Bryan ADRC are to: (l) provide expertise for the diagnosis, prevention, and treatment of dementing illnesses; (2) provide the structure and context for the ascertainment. evaluation, longitudinal follow-up and research participation of large families of AIzheimer's disease (AD) patients; (3) disseminate "unique" tissue and provide needed resources for internal and external research; (4) provide an active clinical center for participation in therapeutic clinical research; and, (5) perform research leading to advances in the biology of AD. The Center's Structure is composed of five interactive Cores: Core A - Administrative Core: Core B - Clinical Research Development Core, Core C - Neuropathology Core including the Rapid Autopsy Protocol (RAP) and a Control Autopsy subunit with the University of Miami: Core D - Education and Information Research Training Core: and Core E - Informatics Core. The Bryan ADRC has built a valuable resource of fresh brain tissue through the RAP. In addition, the Center's accomplishments in molecular genetic studies, specifically the identification of APOE4 as a major genetic susceptibility gene for AD, are now well established. To further clarify the role of APOE4, this application includes five research projects: Project 1 - "Isoform-specific Interactions of ApoE in vitro." W. Strittmatter, PI; Project 2 - "Relationship of ApoE to Neuronal Vulnerability in AD." D. Schmechel, PI; Project 3 - "Subcellular Trafficking of ApoE Isoforms," A. Saunders, PI; Project 4 - "Cellular Processing of ApoE3 and ApoE4," M. Sheetz, PI, and Project 5 - "Production and Analysis of ApoE Transgenic Mice. " J. Gilbert, PI. Two pilot projects are included: Pilot Project 1 - "Neuropsychological-Neuropathological Correlates of AD," M. Murray, PI and Pilot Project 2 - "Dementia Study of the SC Catawba Nation. " F. Allen, PI. The Bryan ADRC has a successful track record for integrating, coordinating, and fostering interdisciplinary cooperation of established and developing investigators. The Bryan ADRC provides for the continued availability of important resources to the local, national, and international environment. These Center resources will continue to strengthen independent and collaborative research efforts, increase productivity, and generate new ideas all aimed at further identification of the cause(s) of AD and other dementing illnesses and the development of prevention, care, and treatment strategies for disease victims and their families.